Expression of proliferating cell nuclear antigen (PCNA) in oral submucous fibrosis, oral epithelial hyperkeratosis and oral epithelial dysplasia in Taiwan

To test whether the oral epithelia of oral submucous fibrosis (OSF), epithelial hyperkeratosis (EH) and epithelial dysplasia (ED) may have increased proliferative activity under the long-term exposure to areca quid ingredients and whether there is an increased expression of proliferating cell nuclear antigen (PCNA) in oral premalignant lesions with disease progression, we used an immunohistochemical technique with the mouse monoclonal antibody PC10 to investigate PCNA expression in histologic sections of OSF, EH, ED and normal oral mucosa (NOM). Positive PCNA staining was found mainly in basal and parabasal epithelial cells in all specimens of OSF, EH, ED and NOM. The mean PCNA labeling indices (LI) in NOM, OSF, EH and ED were 8.8+/-2.7%, 22.1+/-12.5%, 25.5+/-5. 2% and 44.9+/-15.4%, respectively. Significant differences in the PCNA LI were noted between NOM and OSF (P0.01), EH (P0.001) or ED (P0.001), as well as between ED and OSF (P0.001) or EH (P0.01). The gradual increase of PCNA expression with the morphologic transformation of normal epithelial cells into dysplastic epithelial cells suggests that there is increased proliferative activity in oral premalignant lesions with disease progression. However, no significant correlation was found between PCNA LI in OSF epithelium and the clinicohistologic parameters of OSF. In addition, the mean PCNA LI of p53-positive OSF cases (23.7+/-12.0%) was very close to that of p53-negative OSF cases (23.9+/-13.1%), suggesting that there was no association between PCNA and p53 expression in OSF.